The proposed research has three primary goals: to determine if the decrease in energy expenditure associated with reducing diets in obese humans depends on whether the diet is low in fat or low in carbohydrate content; to determine the role of altered thyroid hormone levels and sympathetic nervous system activity in mediating the decrease in energy expenditure; and to compare energy expenditure of obese subjects, before and after weight loss, to that of lean subjects. Obese subjects will be studied while on a weight-maintaining diet, then during weight reduction on a reducing diet (20 kcal/d/kg ideal weight) that contains 20% of energy as protein. Some subjects will be given a low-carbohydrate (5% as energy) and some a low-fat (5% as energy) reducing diet. Energy expenditure will be measured by indirect calorimetry under basal, postprandial, and exercising conditions. The effect of the diets on both protein-bound and free thyroid hormones will be examined, and subjects with a substantial fall in circulating triiodothyronine (T3) levels will be given oral T3 replacement. Sympathetic nervous system activity will be extimated by plasma catecholamine levels and urinary excretion of catecholamine metabolites. The possible role of decreased beta-adrenergic activity in mediating the fall in energy expenditure will be examined by comparing the effect of beta-adrenergic blockade (propranolol) on energy expenditure during weight-maintenance to the effect of propranolol during weight loss. The effects of the different diets on the metabolic intensity rather than loss of active tissue will be determined by expressing energy expenditure per unit of whole-body potassium or whole-body nitrogen. A better understanding of the problems examined in the proposed research may ultimately lead to improved nutritional or pharmacological therapies for treating obesity